Dual Antagonism of PDGF and VEGF in Neovascular Age-Related Macular Degeneration: A Phase IIb, Multicenter, Randomized Controlled Trial

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• 作者：Glenn J. Jaffe ; MD¹ ; ^{jaffe001@mc.duke.edu} ; Thomas A. Ciulla ; MD ; MBA² ; Antonio P. Ciardella ; MD³ ; Francois Devin ; MD⁴ ; Pravin U. Dugel ; MD⁵ ; Chiara M. Eandi ; MD⁶ ; Harvey Masonson ; MD² ; Jordi Moné ; s ; MD ; PhD⁷ ; Joel A. Pearlman ; MD ; PhD⁸ ; Maddalena Quaranta-El Maftouhi ; MD⁹ ; Federico Ricci ; MD¹⁰ ; Keith Westby ; MBA² ; Samir C. Patel ; MD²
• 关键词：AE ; adverse event ; CNV ; choroidal neovascularization ; DA ; disc area ; ETDRS ; Early Treatment Diabetic Retinopathy Study ; FA ; fluorescein angiography ; IOP ; intraocular pressure ; nAMD ; neovascular age-related macular degeneration ; OCT ; optical coherence tomography ; PDGF ; platelet-derived growth factor ; RPE ; retinal pigment epithelium ; SHRM ; subretinal hyperreflective material ; VA ; visual acuity ; VEGF ; vascular endothelial growth factor
• 刊名：Ophthalmology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：124
• 期：2
• 页码：224-234
• 全文大小：1366 K
• 卷排序：124

文摘

To assess the safety and efficacy of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, administered in combination with the anti–vascular endothelial growth factor (VEGF) agent ranibizumab (Lucentis; Roche, Basel, Switzerland) compared with ranibizumab monotherapy in patients with neovascular age-related macular degeneration (nAMD).DesignPhase IIb global, multicenter, randomized, prospective, double-masked, controlled superiority trial.ParticipantsFour hundred forty-nine patients with treatment-naïve nAMD.MethodsParticipants were randomized in a 1:1:1 ratio to 1 of the following 3 intravitreal treatment groups: E10030 0.3 mg in combination with ranibizumab 0.5 mg, E10030 1.5 mg in combination with ranibizumab 0.5 mg, and sham in combination with ranibizumab 0.5 mg (anti-VEGF monotherapy). Drugs were administered monthly in each of the groups for a total duration of 24 weeks.Main Outcome MeasuresThe prespecified primary end point was the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy [ETDRS] letters) from baseline to 24 weeks.ResultsNo significant safety issues were observed in any treatment group. The E10030 (1.5 mg) combination therapy regimen met the prespecified primary end point of superiority in mean VA gain compared with anti-VEGF monotherapy (10.6 compared with 6.5 ETDRS letters at week 24; P = 0.019). A dose-response relationship was evident at each measured time point commencing at 4 weeks. Visual acuity outcomes favored the E10030 1.5 mg combination therapy group regardless of baseline VA, lesion size, or central subfield thickness on optical coherence tomography. All clinically relevant treatment end points of visual benefit (≥15 ETDRS letter gain, final VA ≥20/40 or ≥20/25) and visual loss (≥1 ETDRS line loss, ≥2 ETDRS line loss, final VA ≤20/125 or ≤20/200) favored the E10030 1.5 mg combination group.ConclusionsIn this phase IIb clinical trial, a 62% relative benefit from baseline was noted in the E10030 1.5 mg combination therapy group compared with the anti-VEGF monotherapy group. A favorable safety and efficacy profile of E10030 combination therapy for nAMD was evident across multiple clinically relevant end points. This highly powered study provides strong rationale for a confirmatory phase III clinical trial.